title: Broad and potent cellular and humoral immune responses after a second late HIV-modified vaccinia virus ankara vaccination in HIV-DNA-primed and HIV-modified vaccinia virus Ankara-boosted Swedish vaccinees.
abstract: We have previously shown that an HIV vaccine regimen including three HIV-DNA immunizations and a single HIV-modified vaccinia virus Ankara (MVA) boost was safe and highly immunogenic in Swedish volunteers. A median 38 months after the first HIV-MVA vaccination, 24 volunteers received 10(8) plaque-forming units of HIV-MVA. The vaccine was well tolerated. Two weeks after this HIV-MVA vaccination, 18 (82%) of 22 evaluable vaccinees were interferon (IFN)-γ enzyme-linked immunospot (ELISpot) reactive: 18 to Gag and 10 (45%) to Env. A median minimal epitope count of 4 to Gag or Env was found in a subset of 10 vaccinees. Intracellular cytokine staining revealed CD4(+) and/or CD8(+) T cell responses in 23 (95%) of 24 vaccinees, 19 to Gag and 19 to Env. The frequency of HIV-specific CD4(+) and CD8(+) T cell responses was equally high (75%). A high proportion of CD4(+) and CD8(+) T cell responses to Gag was polyfunctional with production of three or more cytokines (40% and 60%, respectively). Of the Env-specific CD4(+) T cells 40% were polyfunctional. Strong lymphoproliferative responses to Aldrithiol-2 (AT-2)-treated subtype A, B, C, and A_E virus were demonstrable in 21 (95%) of 22 vaccinees. All vaccinees developed binding antibodies to Env and Gag. Neutralizing antibodies were detected in a peripheral blood mononuclear cell (PBMC)-based assay against subtype B and CRF01_AE viruses. The neutralizing antibody response rates were influenced by the vaccine dose and/or mode of delivery used at the previous HIV-MVA vaccination. Thus, a second late HIV-MVA boost induced strong and broad cellular immune responses and improved antibody responses. The data support further exploration of this vaccine concept.
authors.affiliation: 1 Swedish Institute for Communicable Disease Control , Solna, Sweden .
authors.forename: Charlotta
authors.initials: C
authors.lastname: Nilsson
authors.forename: Karina
authors.initials: K
authors.lastname: Godoy-Ramirez
authors.forename: Bo
authors.initials: B
authors.lastname: Hejdeman
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
authors.forename: Lindvi
authors.initials: L
authors.lastname: Gudmundsdotter
authors.forename: David
authors.initials: D
authors.lastname: Hallengärd
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Klara
authors.initials: K
authors.lastname: Hasselrot
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Earl
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Eric
authors.initials: E
authors.lastname: Sandström
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000032:analysis; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D016130:Immunophenotyping; D008297:Male; D013548:Sweden; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D004337:Drug Carriers; D015483:HIV Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic